The tumour immune microenvironment (TIME) plays a critical role in the evolution and progression of cancer. TIME is a highly complex and heterogeneous system that encompasses cells of the immune system and their interactions with the tumour microenvironment. The balance of suppressive versus cytotoxic responses in the tumour microenvironment is balanced by TIME and this can influence disease outcome, with high levels of T cell infiltration associated with better survival in patients. In this series, we explore the impact of TIME on response to cancer treatment and how certain treatments can alter the composition of the TIME and be used in combination with immunotherapy to improve patient outcome.
Join us on 7th December at 10am GMT for the second episode in this three-part series with Dr Eleanor Cheadle, University of Manchester.
- Dr Florent Petitprez, University of Edinburgh, 30th November 10am GMT, B cells, tertiary lymphoid structures, and response to cancer immunotherapy
- Dr Eleanor Cheadle, University of Manchester, 7th December 10am GMT, Investigating how radiotherapy affects the tumour immune microenvironment
- Dr Aideen Ryan, University of Galway, 14th December 10am GMT, Stromal cells and immunosuppression in the tumour microenvironment
Radiotherapy is given to around half of cancer patients as part of their treatment to directly shrink their tumours. There are occasions where radiotherapy given to one tumour lesion can lead to shrinkage of distant non-irradiated lesions, but whilst these incidences of “abscopal effect” are clinically rare, it demonstrates that radiotherapy is able to prime systemic anti-tumour immunity. Furthermore, pre-clinical models show that radiotherapy can be immune-stimulatory with infiltration of T-cells into tumours. However, radiotherapy can also be immunosuppressive with, for example, increased numbers of suppressive myeloid cells infiltrating the tumour microenvironment.
The immune composition of the tumour microenvironment is prognostic in many cancer types, with increased T-cell infiltration associated with greater overall survival. The TME can also predict response to various immunotherapies such as immune checkpoint inhibitors, and pre-clinical data shows that this is also the case for radiotherapy/ immunotherapy combination treatments. Our research is investigating how radiotherapy alters the infiltration of immune cells into the tumour and also what effect it has on systemic immunity. We wish to identify biomarkers which can predict the immune effects of radiotherapy so that we can develop personalised radiotherapy/immunotherapy combination treatments to improve patient outcomes.
- Colton M, Cheadle EJ, Honeychurch J, Illidge TM. Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations. Radiat Oncol. 2020. 15(1):254
- Cheng S, Cheadle EJ, Illidge TM. Understanding the effects of radiotherapy on the tumour immune microenvironment to identify potential prognostic and predictive biomarkers of radiotherapy response. Cancers 2020 12(10):2835
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Dr Eleanor Cheadle undertook her PhD at the University of Leeds from 1999-2002, studying recombinant mycobacterial cancer vaccines and their interaction with dendritic cells and lymphocytes under the supervision of Dr Andrew Jackson and Professor Peter Selby. She then moved to the University of Manchester in 2002, where she began work as a postdoctoral research associate in the group of Professor Robert Hawkins and Dr David Gilham. Her work focused on the generation and testing of chimeric antigen receptor (CAR) T-cells targeting CD19 for use in the treatment of B-cell malignancies. This work led to an ongoing Kay Kendall Leukaemia-funded Phase I clinical trial testing CD19 CAR T-cells in B-cell lymphoma. In 2009 she joined the Targeted Therapy group led by Professor Tim Illidge, and her research has focused on investigating the mechanisms of action of type I and type II anti-CD20 antibodies and improving their efficacy in B-cell malignancies through the use of immunomodulatory agents to enhance adaptive immune responses. In 2018 she took an NIHR BRC-funded post to lead translational science within the Targeted Therapy Group to investigate dynamic immune biomarkers of response to radiotherapy in the tumour microenvironment and systemic circulation.
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